ANALYSIS OF SERUM LEVELS OF THYMIDINE KINASE IN MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE AND MULTIPLE MYELOMA COMPARISON WITH IMAGING Methods 99MTC-MIBI SCINTIGRAPHY AND 18F-FDG PET/CT

Sborník

Background. Proliferation is a independent prognostic factor and target for risk adapted treatment in multiple myeloma. Increased activity of thymidine kinase in serum is associated with higher proliferation rate in hematological malignancies. The imaging methods as 99mTc-MIBI scintigraphy or 18F-FDG PET/CT can imagine active myeloma lesions and their positivity is negative prognostic factor. Materials and MethodsThe analyzed group of 51 patients consisted of 14 (27,5%) individuals with monoclonal gammopathy of undetermined significance (MGUS) and 37 (72,5%) patients with multiple myeloma (MM). There were 25 female (49%) a 26 male (51%) in the group. The average age in the group was 63 years. Thymidine kinase (TK) in serum was evaluated by TK REA and TK ‘the novel technique’ We analyzed correlation of serum TK with biochemical markers reflecting activity of multiple myeloma (MM), e. g. B2M, LDH, free light chains ratio: kappa/lambda K/L, infiltration of bone marrow by plasma cells (Pl. b). The imaging methods as MIBI or PET/CT which imagine active myeloma lesions were done at the time of diagnosis in 20 patients. Results. We found a strong positive correlation between TK values by TK REA and TK ‘the novel technique’(r=0,822). After extreme values were excluded, the correlation coefficient r=0,787. There was clear correlation of serum thymidine kinase with biochemical markers reflecting activity of multiple myeloma (MM), e. g. B2M, LDH, free light chains ratio: kappa/lambda K/L, infiltration of bone marrow by plasma cells (Pl. b). Correlation TK ‘the novel technique’ vs. B2M, LDH, K/L, Pl. b. TK REA - positive correlation of medium strength with B2M (r=0,527) and LDH (r=0,553). TK ‘the novel technique’ - positive correlation of medium strength with B2M (r=0,456), LDH (r=0,573) and weak to positive correlation of medium strength with Pl. b. (r=0,386). Mann- Whitney U test showed at the group of patients with MM (stage I, II or III) significantly higher values of TK REA and TK ‘the novel technique’in comparison to patients in stage MGUS. Median TK REA was 6,0 at MGUS, resp. 9,5 at MM (p=0,004), median TK ‘the novel technique’ was 27,6 at MGUS, resp. 135,9 at MM (p = 0,008). Imaging methods MIBI or PET/CT were positive in 13 patients, and negative in 7 patients. Increased levels of serum thymidine kinase were observed in MIBI or PET/CT positive patients, but correlation did not reached significance level. TK ‘the novel technique’ vs. PET/CT, MIBI (0=negative / 1 or 2 =positive) (without extreme values of TK ‘the novel technique’ Mann-Whitney U test did not show significant difference in values of TK REA or TK ‘the novel technique’ between group of patients with positive and negative PET, MIBI result (p=0,501, resp. p=0,285). AUC = 0,775 - it means TK ‘the novel technique’ could be used as a predictor for multiple myeloma. Conclusions. Statistical analysis revealed significant correlation between serum levels of thymidine kinase and LDH and B2M. Increased levels of serum thymidine kinase were observed in MIBI or PET/CT positive patients, but correlation did not reached significance level.

Supported by grant IGA MZ ČR NT 12215- 4/2011.

Haematologica, 2012; 97(s1):  592